CASC3_HUMAN
ID CASC3_HUMAN Reviewed; 703 AA.
AC O15234; A8K8R0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Protein CASC3;
DE AltName: Full=Cancer susceptibility candidate gene 3 protein;
DE AltName: Full=Metastatic lymph node gene 51 protein {ECO:0000303|PubMed:12080473};
DE Short=MLN 51;
DE AltName: Full=Protein barentsz;
DE Short=Btz;
GN Name=CASC3; Synonyms=MLN51 {ECO:0000303|PubMed:12080473};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary carcinoma;
RX PubMed=7490069; DOI=10.1006/geno.1995.1163;
RA Tomasetto C.L., Regnier C.H., Moog-Lutz C., Mattei M.-G., Chenard M.-P.,
RA Lidereau R., Basset P., Rio M.-C.;
RT "Identification of four novel human genes amplified and overexpressed in
RT breast carcinoma and localized to the q11-q21.3 region of chromosome 17.";
RL Genomics 28:367-376(1995).
RN [2]
RP SEQUENCE REVISION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RC TISSUE=Mammary carcinoma;
RX PubMed=12080473; DOI=10.1038/sj.onc.1205611;
RA Degot S.F., Regnier C.H., Wendling C., Chenard M.-P., Rio M.-C.,
RA Tomasetto C.L.;
RT "Metastatic lymph node 51, a novel nucleo-cytoplasmic protein overexpressed
RT in breast cancer.";
RL Oncogene 21:4422-4434(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Duodenum, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP OVEREXPRESSION IN GASTRIC CANCERS.
RX PubMed=11980659;
RA Varis A., Wolf M., Monni O., Vakkari M.-L., Kokkola A., Moskaluk C.,
RA Frierson H.F. Jr., Powell S.M., Knuutila S., Kallioniemi A., El-Rifai W.;
RT "Targets of gene amplification and overexpression at 17q in gastric
RT cancer.";
RL Cancer Res. 62:2625-2629(2002).
RN [7]
RP INTERACTION WITH MAGOH; NXF1 AND RBM8A, RNA-BINDING, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15166247; DOI=10.1074/jbc.m402754200;
RA Degot S., Le Hir H., Alpy F., Kedinger V., Stoll I., Wendling C.,
RA Seraphin B., Rio M.-C., Tomasetto C.;
RT "Association of the breast cancer protein MLN51 with the exon junction
RT complex via its speckle localizer and RNA binding module.";
RL J. Biol. Chem. 279:33702-33715(2004).
RN [8]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, INTERACTION WITH EIF4A3,
RP MUTAGENESIS OF TYR-181; 184-ARG-LYS-185; PHE-188; TRP-218; 220-HIS-ASP-221
RP AND 240-TYR-GLY-241, SUBCELLULAR LOCATION, AND RNA-BINDING.
RX PubMed=16170325; DOI=10.1038/nsmb990;
RA Ballut L., Marchadier B., Baguet A., Tomasetto C., Seraphin B., Le Hir H.;
RT "The exon junction core complex is locked onto RNA by inhibition of
RT eIF4AIII ATPase activity.";
RL Nat. Struct. Mol. Biol. 12:861-869(2005).
RN [9]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, IDENTIFICATION IN A MRNA
RP SPLICING-DEPENDENT EXON JUNCTION COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16314458; DOI=10.1261/rna.2155905;
RA Tange T.O., Shibuya T., Jurica M.S., Moore M.J.;
RT "Biochemical analysis of the EJC reveals two new factors and a stable
RT tetrameric protein core.";
RL RNA 11:1869-1883(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363 AND SER-373, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP FUNCTION IN STRESS RESPONSE, AND SUBCELLULAR LOCATION.
RX PubMed=17652158; DOI=10.1242/jcs.009225;
RA Baguet A., Degot S., Cougot N., Bertrand E., Chenard M.P., Wendling C.,
RA Kessler P., Le Hir H., Rio M.C., Tomasetto C.;
RT "The exon-junction-complex-component metastatic lymph node 51 functions in
RT stress-granule assembly.";
RL J. Cell Sci. 120:2774-2784(2007).
RN [12]
RP FUNCTION IN EIF4A3 ATPASE AND RNA-HELICASE ACTIVITY.
RX PubMed=17375189; DOI=10.1371/journal.pone.0000303;
RA Noble C.G., Song H.;
RT "MLN51 stimulates the RNA-helicase activity of eIF4AIII.";
RL PLoS ONE 2:E303-E303(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148 AND SER-477, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP ADP-RIBOSYLATION, AND UBIQUITINATION.
RX PubMed=21478859; DOI=10.1038/ncb2222;
RA Zhang Y., Liu S., Mickanin C., Feng Y., Charlat O., Michaud G.A.,
RA Schirle M., Shi X., Hild M., Bauer A., Myer V.E., Finan P.M., Porter J.A.,
RA Huang S.M., Cong F.;
RT "RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin
RT degradation and Wnt signalling.";
RL Nat. Cell Biol. 13:623-629(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-148; SER-265;
RP SER-363 AND SER-373, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-148; SER-265 AND
RP SER-363, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP INTERACTION WITH DHX34.
RX PubMed=25220460; DOI=10.1016/j.celrep.2014.08.020;
RA Hug N., Caceres J.F.;
RT "The RNA helicase DHX34 activates NMD by promoting a transition from the
RT surveillance to the decay-inducing complex.";
RL Cell Rep. 8:1845-1856(2014).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-148 AND THR-357, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 137-286 IN THE EJC COMPLEX WITH
RP EIF4A3; MAGOH; RBM8A AND AMP-PNP.
RX PubMed=16923391; DOI=10.1016/j.cell.2006.08.006;
RA Bono F., Ebert J., Lorentzen E., Conti E.;
RT "The crystal structure of the exon junction complex reveals how it
RT maintains a stable grip on mRNA.";
RL Cell 126:713-725(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 170-246 IN THE EJC COMPLEX WITH
RP EIF4A3; MAGOH; RBM8A AND ADP-NP.
RX PubMed=16931718; DOI=10.1126/science.1131981;
RA Andersen C.B., Ballut L., Johansen J.S., Chamieh H., Nielsen K.H.,
RA Oliveira C.L., Pedersen J.S., Seraphin B., Le Hir H., Andersen G.R.;
RT "Structure of the exon junction core complex with a trapped DEAD-box ATPase
RT bound to RNA.";
RL Science 313:1968-1972(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 138-283 IN THE EJC COMPLEX WITH
RP EIF4A3; MAGOH; RBM8A AND TRANSITION STATE ANALOG ADP-ALF3.
RX PubMed=19033377; DOI=10.1261/rna.1283109;
RA Nielsen K.H., Chamieh H., Andersen C.B., Fredslund F., Hamborg K.,
RA Le Hir H., Andersen G.R.;
RT "Mechanism of ATP turnover inhibition in the EJC.";
RL RNA 15:67-75(2009).
RN [26] {ECO:0007744|PDB:2XB2}
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 137-286 IN THE EJC COMPLEX WITH
RP EIF4A3; MAGOH; RBM8A; UPF3B; UPF2 AND RNA, AND IDENTIFICATION IN THE EJC
RP COMPLEX WITH UPF3A.
RX PubMed=20479275; DOI=10.1073/pnas.1000993107;
RA Buchwald G., Ebert J., Basquin C., Sauliere J., Jayachandran U., Bono F.,
RA Le Hir H., Conti E.;
RT "Insights into the recruitment of the NMD machinery from the crystal
RT structure of a core EJC-UPF3b complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10050-10055(2010).
RN [27] {ECO:0007744|PDB:5XJC}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS), FUNCTION, SUBCELLULAR
RP LOCATION, AND SUBUNIT.
RX PubMed=28502770; DOI=10.1016/j.cell.2017.04.033;
RA Zhang X., Yan C., Hang J., Finci L.I., Lei J., Shi Y.;
RT "An Atomic Structure of the Human Spliceosome.";
RL Cell 169:918-929(2017).
RN [28] {ECO:0007744|PDB:5YZG}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.10 ANGSTROMS), FUNCTION, SUBCELLULAR
RP LOCATION, AND SUBUNIT.
RX PubMed=29301961; DOI=10.1126/science.aar6401;
RA Zhan X., Yan C., Zhang X., Lei J., Shi Y.;
RT "Structure of a human catalytic step I spliceosome.";
RL Science 359:537-545(2018).
CC -!- FUNCTION: Required for pre-mRNA splicing as component of the
CC spliceosome (PubMed:28502770, PubMed:29301961). Core component of the
CC splicing-dependent multiprotein exon junction complex (EJC) deposited
CC at splice junctions on mRNAs. The EJC is a dynamic structure consisting
CC of core proteins and several peripheral nuclear and cytoplasmic
CC associated factors that join the complex only transiently either during
CC EJC assembly or during subsequent mRNA metabolism. The EJC marks the
CC position of the exon-exon junction in the mature mRNA for the gene
CC expression machinery and the core components remain bound to spliced
CC mRNAs throughout all stages of mRNA metabolism thereby influencing
CC downstream processes including nuclear mRNA export, subcellular mRNA
CC localization, translation efficiency and nonsense-mediated mRNA decay
CC (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3.
CC Plays a role in the stress response by participating in cytoplasmic
CC stress granules assembly and by favoring cell recovery following
CC stress. Component of the dendritic ribonucleoprotein particles (RNPs)
CC in hippocampal neurons. May play a role in mRNA transport. Binds
CC spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream
CC of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homomer.
CC {ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:17652158,
CC ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}.
CC -!- SUBUNIT: Identified in the spliceosome C complex (PubMed:28502770,
CC PubMed:29301961). Component of the mRNA splicing-dependent exon
CC junction complex (EJC), which contains at least CASC3, EIF4A3, MAGOH,
CC NXF1 and RBM8A/Y14 (PubMed:15166247, PubMed:16170325, PubMed:16314458,
CC PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275).
CC Identified in a complex composed of the EJC core, UPF3B and UPF2. The
CC EJC core can also interact with UPF3A (in vitro) (PubMed:20479275).
CC Forms homooligomers (By similarity). Interacts with STAU in an RNA-
CC dependent manner (By similarity). Interacts with DHX34; the interaction
CC is RNA-independent (PubMed:25220460). {ECO:0000250|UniProtKB:Q8K3X0,
CC ECO:0000269|PubMed:15166247, ECO:0000269|PubMed:16170325,
CC ECO:0000269|PubMed:16314458, ECO:0000269|PubMed:16923391,
CC ECO:0000269|PubMed:16931718, ECO:0000269|PubMed:19033377,
CC ECO:0000269|PubMed:20479275, ECO:0000269|PubMed:25220460,
CC ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}.
CC -!- INTERACTION:
CC O15234; P38919: EIF4A3; NbExp=33; IntAct=EBI-299118, EBI-299104;
CC O15234; Q3LI66: KRTAP6-2; NbExp=5; IntAct=EBI-299118, EBI-11962084;
CC O15234; P61326: MAGOH; NbExp=24; IntAct=EBI-299118, EBI-299134;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12080473}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q8K3W3}. Nucleus
CC {ECO:0000269|PubMed:12080473, ECO:0000269|PubMed:28502770,
CC ECO:0000269|PubMed:29301961}. Nucleus speckle
CC {ECO:0000269|PubMed:16170325}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:17652158}. Cytoplasm, Cytoplasmic ribonucleoprotein
CC granule {ECO:0000250|UniProtKB:Q8K3X0}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q8K3X0}. Note=Shuttles between the nucleus and
CC the cytoplasm in a XPO1/CRM1-dependent manner. Transported to the
CC cytoplasm as part of the exon junction complex (EJC) bound to mRNA
CC (PubMed:15166247). In nuclear speckles, colocalizes with MAGOH. Under
CC stress conditions, colocalizes with FMR1 and TIA1, but not MAGOH and
CC RBM8A EJC core factors, in cytoplasmic stress granules
CC (PubMed:17652158). In the dendrites of hippocampal neurons, localizes
CC to dendritic ribonucleoprotein granules (By similarity).
CC {ECO:0000250|UniProtKB:Q8K3X0, ECO:0000269|PubMed:15166247,
CC ECO:0000269|PubMed:17652158}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Overexpressed in breast cancers
CC and metastasis, as well as in gastric cancers.
CC {ECO:0000269|PubMed:12080473}.
CC -!- DOMAIN: The coiled coil domain may be involved in oligomerization.
CC -!- PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated
CC protein is recognized by RNF146, followed by ubiquitination.
CC {ECO:0000269|PubMed:21478859}.
CC -!- PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its
CC degradation. {ECO:0000269|PubMed:21478859}.
CC -!- SIMILARITY: Belongs to the CASC3 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MLN51ID241.html";
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DR EMBL; X80199; CAC27699.1; -; mRNA.
DR EMBL; AK292425; BAF85114.1; -; mRNA.
DR EMBL; AC068669; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044656; AAH44656.1; -; mRNA.
DR EMBL; BC050526; AAH50526.1; -; mRNA.
DR CCDS; CCDS11362.1; -.
DR RefSeq; NP_031385.2; NM_007359.4.
DR RefSeq; XP_005257220.1; XM_005257163.1.
DR PDB; 2HYI; X-ray; 2.30 A; D/J=170-246.
DR PDB; 2J0Q; X-ray; 3.20 A; I/T=137-286.
DR PDB; 2J0S; X-ray; 2.21 A; T=137-286.
DR PDB; 2J0U; X-ray; 3.00 A; T=137-250.
DR PDB; 2XB2; X-ray; 3.40 A; S/T=137-286.
DR PDB; 3EX7; X-ray; 2.30 A; D/I=138-283.
DR PDB; 5XJC; EM; 3.60 A; x=1-703.
DR PDB; 5YZG; EM; 4.10 A; x=1-703.
DR PDB; 6ICZ; EM; 3.00 A; x=1-703.
DR PDBsum; 2HYI; -.
DR PDBsum; 2J0Q; -.
DR PDBsum; 2J0S; -.
DR PDBsum; 2J0U; -.
DR PDBsum; 2XB2; -.
DR PDBsum; 3EX7; -.
DR PDBsum; 5XJC; -.
DR PDBsum; 5YZG; -.
DR PDBsum; 6ICZ; -.
DR AlphaFoldDB; O15234; -.
DR SMR; O15234; -.
DR BioGRID; 116475; 124.
DR ComplexPortal; CPX-1941; Exon junction core complex, MAGOH variant.
DR ComplexPortal; CPX-682; Exon junction core complex, MAGOHB variant.
DR CORUM; O15234; -.
DR DIP; DIP-33288N; -.
DR ELM; O15234; -.
DR IntAct; O15234; 55.
DR MINT; O15234; -.
DR STRING; 9606.ENSP00000264645; -.
DR TCDB; 3.A.18.1.1; the nuclear mrna exporter (mrna-e) family.
DR GlyGen; O15234; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15234; -.
DR PhosphoSitePlus; O15234; -.
DR BioMuta; CASC3; -.
DR EPD; O15234; -.
DR jPOST; O15234; -.
DR MassIVE; O15234; -.
DR MaxQB; O15234; -.
DR PaxDb; O15234; -.
DR PeptideAtlas; O15234; -.
DR PRIDE; O15234; -.
DR ProteomicsDB; 48528; -.
DR TopDownProteomics; O15234; -.
DR Antibodypedia; 16438; 290 antibodies from 29 providers.
DR DNASU; 22794; -.
DR Ensembl; ENST00000264645.12; ENSP00000264645.6; ENSG00000108349.17.
DR GeneID; 22794; -.
DR KEGG; hsa:22794; -.
DR MANE-Select; ENST00000264645.12; ENSP00000264645.6; NM_007359.5; NP_031385.2.
DR UCSC; uc002hue.4; human.
DR CTD; 22794; -.
DR DisGeNET; 22794; -.
DR GeneCards; CASC3; -.
DR HGNC; HGNC:17040; CASC3.
DR HPA; ENSG00000108349; Low tissue specificity.
DR MIM; 606504; gene.
DR neXtProt; NX_O15234; -.
DR OpenTargets; ENSG00000108349; -.
DR PharmGKB; PA134948596; -.
DR VEuPathDB; HostDB:ENSG00000108349; -.
DR eggNOG; KOG4264; Eukaryota.
DR GeneTree; ENSGT00390000006930; -.
DR HOGENOM; CLU_018976_0_0_1; -.
DR InParanoid; O15234; -.
DR OMA; MIQDPHM; -.
DR OrthoDB; 486761at2759; -.
DR PhylomeDB; O15234; -.
DR TreeFam; TF329663; -.
DR PathwayCommons; O15234; -.
DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR SignaLink; O15234; -.
DR SIGNOR; O15234; -.
DR BioGRID-ORCS; 22794; 119 hits in 1094 CRISPR screens.
DR ChiTaRS; CASC3; human.
DR EvolutionaryTrace; O15234; -.
DR GeneWiki; CASC3; -.
DR GenomeRNAi; 22794; -.
DR Pharos; O15234; Tbio.
DR PRO; PR:O15234; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O15234; protein.
DR Bgee; ENSG00000108349; Expressed in sural nerve and 202 other tissues.
DR ExpressionAtlas; O15234; baseline and differential.
DR Genevisible; O15234; HS.
DR GO; GO:0010494; C:cytoplasmic stress granule; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0071006; C:U2-type catalytic step 1 spliceosome; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0003729; F:mRNA binding; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0008298; P:intracellular mRNA localization; IEA:Ensembl.
DR GO; GO:0006406; P:mRNA export from nucleus; IC:ComplexPortal.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW.
DR GO; GO:2000622; P:regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:ComplexPortal.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR DisProt; DP02170; -.
DR IDEAL; IID00185; -.
DR InterPro; IPR018545; Btz_dom.
DR InterPro; IPR028544; CASC3.
DR PANTHER; PTHR13434; PTHR13434; 1.
DR Pfam; PF09405; Btz; 1.
DR SMART; SM01044; Btz; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Cell projection; Coiled coil; Cytoplasm;
KW mRNA processing; mRNA splicing; mRNA transport;
KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; Spliceosome; Stress response; Translation regulation;
KW Transport; Ubl conjugation.
FT CHAIN 1..703
FT /note="Protein CASC3"
FT /id="PRO_0000089324"
FT REGION 1..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..283
FT /note="Necessary for RNA-binding, interaction with MAGOH
FT and localization in nucleus speckles"
FT /evidence="ECO:0000269|PubMed:15166247"
FT REGION 137..283
FT /note="Sufficient to form the EJC"
FT REGION 377..703
FT /note="Necessary for localization in cytoplasmic stress
FT granules"
FT REGION 492..538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 633..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 95..131
FT /evidence="ECO:0000255"
FT MOTIF 204..210
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000255"
FT MOTIF 254..262
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000255"
FT MOTIF 462..466
FT /note="Nuclear export signal"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..108
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..141
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..232
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..360
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..418
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..443
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..462
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 637..653
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 654..673
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..694
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K3W3"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 357
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MUTAGEN 181
FT /note="Y->A: Does not affect EJC formation."
FT /evidence="ECO:0000269|PubMed:16170325"
FT MUTAGEN 184..185
FT /note="RK->AA: Does not affect EJC formation."
FT /evidence="ECO:0000269|PubMed:16170325"
FT MUTAGEN 188
FT /note="F->A: Does not affect EJC formation."
FT /evidence="ECO:0000269|PubMed:16170325"
FT MUTAGEN 218
FT /note="W->A: Abolishes interaction with EIF4A3, EJC
FT formation and localization in nucleus speckles."
FT /evidence="ECO:0000269|PubMed:16170325"
FT MUTAGEN 220..221
FT /note="HD->AA: Abolishes interaction with EIF4A3, EJC
FT formation and localization in nucleus speckles."
FT /evidence="ECO:0000269|PubMed:16170325"
FT MUTAGEN 240..241
FT /note="YG->AA: Abolishes interaction with EIF4A3, EJC
FT formation and localization in nucleus speckles."
FT /evidence="ECO:0000269|PubMed:16170325"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:2J0S"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:2J0S"
FT HELIX 233..240
FT /evidence="ECO:0007829|PDB:2HYI"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:3EX7"
SQ SEQUENCE 703 AA; 76278 MW; 642A4C01C8DD3BE0 CRC64;
MADRRRQRAS QDTEDEESGA SGSDSGGSPL RGGGSCSGSA GGGGSGSLPS QRGGRTGALH
LRRVESGGAK SAEESECESE DGIEGDAVLS DYESAEDSEG EEGEYSEEEN SKVELKSEAN
DAVNSSTKEE KGEEKPDTKS TVTGERQSGD GQESTEPVEN KVGKKGPKHL DDDEDRKNPA
YIPRKGLFFE HDLRGQTQEE EVRPKGRQRK LWKDEGRWEH DKFREDEQAP KSRQELIALY
GYDIRSAHNP DDIKPRRIRK PRYGSPPQRD PNWNGERLNK SHRHQGLGGT LPPRTFINRN
AAGTGRMSAP RNYSRSGGFK EGRAGFRPVE AGGQHGGRSG ETVKHEISYR SRRLEQTSVR
DPSPEADAPV LGSPEKEEAA SEPPAAAPDA APPPPDRPIE KKSYSRARRT RTKVGDAVKL
AEEVPPPPEG LIPAPPVPET TPTPPTKTGT WEAPVDSSTS GLEQDVAQLN IAEQNWSPGQ
PSFLQPRELR GMPNHIHMGA GPPPQFNRME EMGVQGGRAK RYSSQRQRPV PEPPAPPVHI
SIMEGHYYDP LQFQGPIYTH GDSPAPLPPQ GMLVQPGMNL PHPGLHPHQT PAPLPNPGLY
PPPVSMSPGQ PPPQQLLAPT YFSAPGVMNF GNPSYPYAPG ALPPPPPPHL YPNTQAPSQV
YGGVTYYNPA QQQVQPKPSP PRRTPQPVTI KPPPPEVVSR GSS
